Publications by Year: 2018

2018
Avgerinos KI, Spyrou N, Mantzoros CS, Dalamaga M. Obesity and Cancer Risk: Emerging biological mechanisms and perspectives. Metabolism. 2018.Abstract
Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype.
Emfietzoglou R, Spyrou N, Mantzoros CS, Dalamaga M. Could the endocrine disruptor bisphenol-a be implicated in the pathogenesis of oral and oropharyngeal cancer? Metabolic conisderations and future directions. Metabolism. 2018.Abstract
Bisphenol-A (BPA), a prototype endocrine disrupting molecule, has been associated with many disease entities such as diabetes mellitus, obesity, polycystic ovarian disease, cardiovascular disease, reproductive and neurodevelopmental disorders. BPA has also been associated mainly with hormone sensitive cancers such as breast, prostate, endometrial, ovarian, testicular and thyroid cancers but also non-hormonal sensitive cancers such as cervical and lung cancers, osteosarcoma and meningioma. Recent research has investigated the sources of contamination which are responsible for higher BPA concentrations in the oral cavity and oropharyngeal space, representing the first site of BPA exposure after ingestion. Besides growing awareness and case registration, the incidence and prevalence of oral (OC) and oropharyngeal cancer (OPC) have increased during the last decades correlating with the increased production of BPA worldwide. So far, no study in the medical literature has explored the association of BPA with OC and OPC. BPA may be linked to the etiopathogenesis of OC and OPC through a multitude of mechanisms encompassing and interconnecting genetic, epigenetic, inflammatory, immune, metabolic, hormonal and oxidative stress alterations as well as modulation of oral microbiome. Hence, it is not possible to rule out a potential role of BPA exposure in oral and oropharyngeal tissue carcinogenesis, especially knowing its potential to participate in other non hormonal sensitive malignancies and to deregulate signaling pathways implicated in OC and OPC. This perspective aims at outlining evidence and proposing for the first time a potential link between BPA with OC and OPC, the most frequent subtypes of head and neck malignancies.
Sotiropoulos GP, Dalamaga M, Antonakos G, Marinou I, Vogiatzakis E, Kotopouli M, Karampela I, Christodoulatos GS, Lekka A, Papavassiliou AG. Chemerin as a biomarker at the intersection of inflammation, hemotaxis, coagulation, fibrinolysis and metabolism in resectable non-small cell lung cancer. Lung Cancer. 2018;125:291-299.Abstract
OBJECTIVES: Chemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. MATERIALS AND METHODS: In a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month). RESULTS: NSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09-4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 μg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC. CONCLUSION: Chemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data.
Spyrou N, Avgerinos KI, Mantzoros CS, Dalamaga M. Classic and Novel Adipocytocines at the Intersection of Obesity and Cancer: Diagnostic and Therapeutic Strategies. Curr Obes Rep. 2018;7(4):260-275.Abstract
PURPOSE OF REVIEW: In this review, we investigate the role of classic and novel adipocytokines in cancer pathogenesis synopsizing the mechanisms underlying the association between adipocytokines and malignancy. Special emphasis is given on novel adipocytokines as new evidence is emerging regarding their entanglement in neoplastic development. RECENT FINDINGS: Recent data have emphasized the role of the triad of overweight/obesity, insulin resistance and adipocytokines in cancer. In the setting of obesity, classic and novel adipocytokines present independent and joint effects on activation of major intracellular signaling pathways implicated in cell proliferation, expansion, survival, adhesion, invasion, and metastasis. Until now, more than 15 adipocytokines have been associated with cancer, and this list continues to expand. While the plethora of circulating pro-inflammatory adipocytokines, such as leptin, resistin, extracellular nicotinamide phosphoribosyl transferase, and chemerin are elevated in malignancies, some adipocytokines such as adiponectin and omentin-1 are generally decreased in cancers and are considered protective against carcinogenesis. Elucidating the intertwining of inflammation, cellular bioenergetics, and adiposopathy is significant for the development of preventive, diagnostic, and therapeutic strategies against cancer. Novel more effective and safe adipocytokine-centered therapeutic interventions may pave the way for targeted oncotherapy.
I K, Tzortzis E, Nikolopoulos M, Dalamaga M, Diomidous M, Armaganidis A. A Hospital Information System Application May Facilitate Staff Compliance with Quality Protocols in a Medical Unit: A Case Study. Stud Health Technol Inform. 2018;251:203-206.Abstract
Quality standards have been widely adopted in healthcare, while the Hospital Information Systems (HIS) support quality management in modern hospitals. However, staff compliance lags behind. In this study, we investigated the effect of a novel application, implemented in the HIS, on staff compliance in the Intensive Care Unit of a tertiary teaching hospital. This application integrates quality protocols to the HIS, which is routinely used by the nursing staff. Demographic data and self-reported compliance were recorded before and after the intervention. We found that the compliance rate was significantly increased and the application was well accepted by the majority of the staff. We also showed that previous ICU working experience is independently and positively associated with compliance (p=0.02, OR=2.86; 95% CI: 1.16 - 7.06), after adjustment for age and total nursing experience In conclusion, we developed an effective application for quality improvement aiming at facilitating educational processes and enhancing staff compliance.
Nikolopoulos M, Karampela I, Tzortzis E, Dalamaga M. Deploying Cloud Computing in the Greek Healthcare System: A Modern Development Proposal Incorporating Clinical and Laboratory Data. Stud Health Technol Inform. 2018;251:35-38.Abstract
Cloud computing is a reality in most business sectors. Hospitals have been more reluctant to adopt cloud technology due to strict data security regulations. Cloud could provide economies of scale reducing Information Technology spending in the Greek state-owned hospitals, while giving the opportunity to the hospitals to upgrade their profile offering web-based services. We propose a simple, robust and easy to apply approach for the Greek hospitals, focusing on clinical and laboratory data in order to move to the cloud environment. To the best of our knowledge, there is no other study regarding the adoption of cloud infrastructure in the Greek hospital sector. This innovative method could transform the business model of the hospitals.
Stratigou T, Dalamaga M, Antonakos G, Marinou I, Vogiatzakis E, Christodoulatos GS, Karampela I, Papavassiliou AG. Hyperirisinemia is independently associated with subxlinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors. Endocrine. 2018;61(1):83-93.Abstract
PURPOSE: Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors. METHODS: In a large case-control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed. RESULTS: SH cases exhibited significantly higher circulating irisin than controls (p < 0.001). In all participants, irisin was positively associated with TSH, anti-TG, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, leptin, and cardiovascular risk factors, including Framigham score and apolipoprotein B/apolipoprotein A-I. Irisin was negatively correlated with adiponectin, HDL-C, and thyroid hormones. Serum irisin was independently associated with SH, above and beyond body mass index and cardiometabolic factors (p = 0.02). TSH was an independent predictor of circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the hyperirisinemic status in treated SH patients (p = 0.09). CONCLUSIONS: Irisin may represent an adipo-myokine counterbalancing a potential, gradual deterioration of lipid metabolism and insulin sensitivity in SH as well as reflecting a protective compensatory mechanism against oxidative muscle and thyroid cell stress. More mechanistic and prospective studies shedding light on the pathogenetic role of irisin in SH are needed to confirm and extend these data.
Dalamaga M, Christodoulatos GS, Mantzoros CS. The role of extracellular and intracellular Nicotinamide phosphoribosyl-transferase in cancer: Diagnostic and therapeutic perspectives and challenges. Metabolism. 2018;82:72-87.Abstract
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties. Nampt is upregulated in many malignancies, including obesity-associated cancers, and is associated with worse prognosis. Serum Nampt may be a potential diagnostic and prognostic biomarker in cancer. Pharmacologic agents that neutralize Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer treatments. In particular, Nampt inhibitors as monotherapy or in combination therapy have displayed anti-cancer activity in vivo and in vitro. The aim of this review is to explore the role of Nampt in cancer pathophysiology as well as to synopsize the mechanisms underlying the association between extracellular and intracellular Nampt, and malignancy. Exploring the interplay of cellular bioenergetics, inflammation and adiposopathy is expected to be of importance in the development of preventive and therapeutic strategies against cancer.
Dalamaga M, Karampela I. Fetuin-A to adiponecting ratio is a promising prognostic biomarker in septic critically ill patients. J Crit Care. 2018;44:134-135.